In a principal aspect the present invention relates to two major problems facing current dental composites; namely, secondary caries and bulk fracture. The invention is directed to new dental materials that overcome these problems by being extremely strong mechanically to resist fracture and by being able to simultaneously release agents to combat caries.
Specifically, an object of the invention is to (1) provide new dental materials having nano calcium phosphate and/or other fillers capable of substantial release of calcium, phosphate and/or fluoride to combat tooth decay; (2) tailor the nano releasing filler/strengthening filler ratio and the fast releasing filler/slow releasing filler ratio to control the release profile and provide superior resistance to chewing forces; and (3) provide novel compositions for dental restorations, stress-bearing applications, artificial crowns, anterior and posterior tooth fillings, adhesives, cavity liners, cements, bases, orthodontic devices, prostheses, and sealants.
The new materials are substantially stronger than currently available stress-bearing composites, yet the new composites include release agents useful to combat tooth caries, while the currently available stress-bearing composites do not.
That is, known current composites that do possess release capabilities for calcium and phosphate, etc. are too weak mechanically for large stress-bearing applications. The new composites are not only much stronger, but can also release more calcium and phosphate ions than known prior art composites.
Dental composites are composed of a mixture of fillers with a hardenable matrix, for example, an acrylic monomer (also termed resin or dental resin), that is polymerized or hardened to form a composite restoration. The two most major clinical problems of current dental composites have been: restoration fracture, and secondary caries. A recent review article shows that “clinical data indicate that the two main challenges are secondary caries and bulk fracture” (Sarrett, Clinical challenges and the relevance of materials testing for posterior composite restorations, Dent Mater, 21:9-20, 2005).
Two classes of dental materials have been developed to address these issues. The first class is termed stress-bearing materials, and the second class is termed releasing materials. Stress-bearing materials include dental composites that are developed with the purpose of being used in large stress-bearing restorations. Releasing materials release calcium, phosphate, fluoride and other agents to prevent tooth decay and to repair or remineralize tooth structures that have already decayed or lost tooth minerals.
Problem I. Restoration Fracture
Stress-bearing dental composites have been significantly enhanced (for example, see Ferracane et al., J Biomed Mater Res 42:465-472, 1998). However, dental composites “are not recommended for large posterior restorations because of the potential for excessive wear, microleakage or fracture” (Bayne et al., J Am Dent Assoc 125:687-701, 1994). For filled polymer composite crowns, fracture during service has been observed and the composites have lost favor as they continued to fail (Christensen, J Am Dent Assoc 130:409-411, 1999). Even for small inlay restorations, while the 7-year clinical failure rate of a composite for premolar inlays was relatively low, nearly half of the stress-bearing molar inlays had failed at 7 years (Donly et al., Quintessence Intl 30:163-169, 1999). Therefore, it is recognized that “some properties might be satisfactory for smaller restorations, but insufficient for larger restorations” (Sakaguchi, Dent Mater 21:3-6, 2005).
The strength of dental composites is generally considered to be adequately measured in a flexural test. Although the direct measurement of tensile strength may have validity, it is technically difficult to execute. The compressive strength is only indirectly related, in a complex manner, to a combination of tensile and shear failure modes. The measurement of diametral tensile strength requires that the material exhibits no plastic flow, which does not hold true for the majority of dental composites. Therefore, the flexural test has been utilized to characterize the mechanical properties of dental composites. Currently-available dental composites for stress-bearing restorations usually have flexural strength values ranging from 80 MPa (1 MPa=106 N/m2; N=Newton, m=meter) to about 120 MPa (Xu et al., J Dent Res 78:706-712, 1999). Their fracture toughness (resistance to cracking) ranges from about 0.9 MPa·m1/2 to 1.1 MPa·m1/2 (Xu, J Dent Res 79:1392-1397, 2000). Further improvements are needed for composites to overcome brittle fracture and high failure rates in high stress-bearing restorations (Christensen, J Am Dent Assoc 130:409-411, 1999; Donly et al., Quintessence Intl 30:163-169, 1999), especially those that are large in restoration size and involve the replacement of tooth cusps.
Problem II. Secondary Caries
The terms “caries”, “cavities” and “tooth decay” refer to the demineralization or dissolution of tooth mineral. The term “demineralization” refers to the loss of mineral in tooth structure, resulting in mineral-deficient lesions. The terms “remineralization”, “mineralization” and similar terms mean the formation of solid inorganic structures similar to the mineral in natural teeth. “Secondary caries” refers to the recurrence of demineralization at a certain period of time after the primary caries is removed and the tooth cavity is restored.
Secondary caries is often cited as a major reason for the replacement of existing composite restorations (Sarrett, Dent Mater, 21:9-20, 2005). Glass ionomers, resin-modified glass ionomers and compomers are developed to release fluoride into adjacent tooth structure to combat caries. Glass ionomers refer to dental materials that are based on the acid-base reaction of an aqueous solution of a polycarboxylic acid with an ion leachable, fluoride-containing glass. However, the brittleness and inferior mechanical properties of glass ionomers (flexural strength of 10-20 MPa) have severely limited their use. Resin-modified glass ionomers use resins (for example, 2-hydroxyethyl methacrylate, or HEMA) with the polyacids. The name compomer is derived by combining the two words composite and ionomer, and is intended to suggest a combination of composite and glass-ionomer technology. They are modified in their resin phase by a carboxylic acid monomer, and in their filler phase by the inclusion of an acid-reactive, ion-leachable glass. Resin-modified glass ionomers and compomers are not recommended for use in large, stress-bearing restorations.
Other materials release calcium (Ca2+) and phosphate (PO4) ions to form hydroxyapatite (HA), Ca10(PO4)6(OH)2, which is the putative mineral in natural teeth (Skrtic et al., J Dent Res 75:1679-1686, 1996; Dickens et al., Dent Mater 19:558-566, 2003). These materials are highly promising for remineralizing the decayed teeth and help prevent the occurrence of caries. These novel composites possess diametral tensile strength of 10 MPa to 30 MPa, and flexural strength of 50 MPa to 70 MPa. While their calcium and phosphate release have excellent remineralization capability, these composites are not strong enough for use in large-stress restorations or fillings that replace tooth cusps.
U.S. Pat. No. 4,612,053 (Brown et al.) and U.S. Pat. No. 5,695,729 (Chow et al.) disclose self-setting calcium phosphate cements (CPC) consisting of tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrous (DCPA) or dihydrate (DCPD). U.S. Pat. No. 5,652,016 (Imura et al.) discloses calcium phosphate cement compositions. CPCs are excellent bone repair materials because they can harden in situ in the bone cavity. Hydroxyapatite is relatively stable with minimal release of calcium and phosphate ions, hence CPC is not being used to remineralize decayed tooth structures. In addition, there is no mention of using CPC in large stress-bearing tooth restorations. This is because the flexural strength of about 10 MPa for CPC is not generally sufficient to survive the chewing forces.
U.S. Pat. No. 4,813,876 (Wang) discloses calcium hydroxide-containing polymerizable cavity liner. Because it does not have a phosphate component, it does not teach the remineralization capacity to form hydroxyapatite.
U.S. Pat. No. 5,508,342 (Antonucci et al.) discloses polymeric releasing compositions containing amorphous calcium phosphate (ACP). They release calcium and phosphate ions with concentrations of about 1.0 mmol/L (=10−3 mole/liter) for calcium and 0.25-0.8 mmol/L for phosphate ions. These composites are highly promising for remineralizing decayed tooth structures and in preventing demineralization. However, there are three drawbacks. First, the ACP powders are weak mechanically, hence it is recognized that they do not act as reinforcing fillers (Skrtic et al., J Biomed Mater Res Appl Biomater 53:381-391, 2000). Second, the low filler level (inorganic/[inorganic+hardenable matrix]) of 40% mass fraction means that the composite consists of mostly resin. Low filler level results in high polymerization shrinkage, yielding undesirable internal stresses in the tooth cavity. Third, flexural strength of 50-70 MPa for the ACP composite is relatively low compared to 80-120 MPa for currently available stress-bearing composites. Even the latter exhibit bulk fracture in large stress-bearing restorations. Hence these releasing materials do not have the fracture toughness and wear resistance to resist chewing forces for large cavities or load-bearing restorations.
U.S. Pat. No. 5,814,681 (Hino et al.) discloses a composition containing calcium phosphate powder and polymerizable monomer. It is for bone repair. There is no mention of calcium and phosphate release nor remineralization of tooth structures.
U.S. Pat. No. 6,398,859 discloses resin-based pulp-capping and remineralizing cements. Examples of cements comprise the combination of a paste 1 and either a paste 2 or a powder, wherein paste 1 contains dicalcium phosphate and other components, and paste 2 or the powder contains tetracalcium phosphate. This material not only exhibits a high pH of around 10 during hardening to stimulate new dentin formation in pulp capping, but also releases calcium and phosphate ions to form hydroxyapatite and remineralize decayed tooth structures. Therefore, it has the excellent ability to act in the dual manner as a pulp capping cement while simultaneously promoting the repair of mineral-deficient tooth structure through the precipitation of tooth-like minerals. Its diametral tensile strength of 10-30 MPa is sufficient for pulp capping applications. These materials release concentrations of about 0.05-0.5 mmol/L of calcium and 0.3-1.0 mmol/L of phosphate ions (Dickens et al., Dental Materials 19:558-566, 2003). These materials are for pulp-capping and base/lining cement and other dental cements applications. They are not suggested for large stress-bearing restorations, wear-resistant restorations, or fillings that involve tooth cusps.
U.S. Pat. No. 5,861,445 (Xu et al.) and U.S. Pat. No. 6,334,775 (Xu et al.) disclose dental composites containing whiskers and fibers within a hardenable matrix. There is no mention of using nano-sized calcium phosphate fillers or the release of calcium and phosphate ions for the remineralization of decayed tooth structures. There is no teaching of a method of controlling the Ca2+ and PO4 release profile by tailoring the nano releasing filler/strengthening filler ratio or the fast releasing filler/slow releasing filler ratio.
U.S. Pat. application 20020156152 (Zhang et al.) and application 20030181541 (Wu et al.) disclose dental materials with nano-sized silica particles. Diametral tensile strength of 62-68 MPa is achieved. There is no mention of using calcium and phosphate fillers; there is no release of calcium and phosphate ions; and there is no teaching on remineralization of decayed teeth.
U.S. Pat. application 20030147956 (Shefer et al.) discloses controlled release for site specific delivery of biologically active ingredients for oral care. It is not related to tooth cavity fillings and restorations, nor is it related to polymers and resin composites.
U.S. Pat. application 20040086446 (Jia et al.) discloses dental resin materials with nano silica fillers. There is no mention of using nano-sized calcium phosphate fillers, and there is no teaching of remineralizing the decayed tooth structures.
Prior art, stress-bearing composites appear to have flexural strength of 80-120 MPa, but do not have calcium or phosphate ion release. They can survive in moderate-stress applications, but they exhibit bulk fracture in large stress-bearing restorations, especially those that involve tooth cusps. Releasing composites have strengths of 30-70 MPa. There is no description, of dental composites that have flexural strength of 140-170 MPa together with substantial release, which are described in this application which are not only 100%-500% higher than the releasing composites in the prior art, but also 40%-100% higher than the stress-bearing composites without release as reported by prior art.
In addition, in the prior art, the releasing materials release calcium and phosphate at concentrations of 0.1 to 1 mmol/L. There is no mention of dental composites that release calcium and phosphate ions with concentrations of 2 to 7 mmol/L and as high as 16 mmol/L. Such new dental composites are described in the present application.